The techniques of rapid reaction kinetics will be employed to study the mechanism of oxygen binding to normal and abnormal hemoglobins. The proposed studies are a continuation of an effort to obtain elementary rate and equilibrium constants for individual subunits within tetrameric hemoglobin and to determine quantitatively the effect of organic phosphates on each subunit rate parameter. A recently observed DPG-induced spectroscopic change in liganded hemoglobin will be investigated by methods that will provide information about possible iron spin-state changes. The mechanism by which N-terminal specific modifications of hemoglobin-S inhibit gellation will be studied after isolation of the various N-terminal modified tetramer intermediates. A method will be developed for measuring the rate of the initial stages of Hb-S association.